by applicant): Ricin and Shiga toxin are among the most potent poisons known. They are able to kill mammalian cells by catalytically inactivating ribosomes. This entails binding to cell surface receptors, endocytic uptake, and intracellular trafficking to reach a compartment.from which the catalytic fragment translocates into the cytosol where its substrate is located. Because of this, they pose a serious threat to human health, a threat recently extended by their potential use as agents for bioterrorism. At the moment, no effective inhibitors or vaccines are available to combat this danger. The proposed program is a combination of four complementary research projects aimed at overcoming these limitations: a) Developing vaccines. Current vaccination approaches may be limited in the case of ricin because they involve modification of the active